Download CORTISOL

CORTITROL STRESS CONTROL FORMULA™
- TECHNICAL PRODUCT BULLETIN –
(HEALTHCARE PROFESSIONALS VERSION)
SUMMARY
Cortitrol Stress Control Formula™ is a dietary supplement developed and manufactured by Pharmanex,
LLC, to help the body modulate healthy levels of cortisol. This revolutionary product is a patent-pending
cortisol-controlling dietary supplement that combines natural ingredients that have been scientifically
shown to have direct cortisol-balancing effects. Ingredients included in Pharmanex Cortitrol that may have
cortisol-lowering effects include magnolia bark (Magnolia officinalis), epimedium (Epimedium koreanum),
theanine, beta sitosterol and phosphatidylserine.
This technical bulletin reviews the scientific rationale behind the formulation of Cortitrol. It also discusses
the purported health benefits, mechanisms of action, published scientific studies, and proprietary
processing. This is an educational bulletin provided to help licensed healthcare professionals understand the
science upon which Cortitrol is based. This bulletin should not be used to sell Cortitrol, and it should be
distributed only to licensed healthcare professionals. The only claims that can be made for Cortitrol are
those that have been approved by Pharmanex.
ABOUT CORTISOL
Cortisol, also known as Cortisone and Hydrocortisone, is a steroid hormone
produced in the adrenal gland in response to stress. As such, cortisol is often
referred to as the primary “stress hormone.” In the body, cortisol is needed to
maintain normal physiological processes during times of stress—without
cortisol, the body would not be able to respond effectively to stress. With an
effective cortisol metabolism, cortisol secretion releases amino acids from
muscle, glucose from the liver and fatty acids from adipose tissue into the
blood stream for use as energy.
1. Stress causes the
hypothalamus to secrete
Corticotropin Releasing
Hormone (CRH).
2. CRH travels to the pituitary
gland and causes secretion of
Adreno-Cortico-Tropic Hormone
(ACTH) into the blood.
3. ACTH reaches the adrenal glands
(above kidneys) and causes secretion
of Cortisol .
CORTISOL
*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure or prevent any disease.
Normal cortisol metabolism undergoes a “diurnal rhythm,” meaning that cortisol levels vary throughout a
24-hour period with the highest levels typically observed in the early morning and the lowest levels in the
early hours (about midnight – 2 am). Cortisol levels usually show a rapid drop between 8 am and 11 am
and a continued gradual decline throughout the day. From those lowest levels around 2 am, cortisol again
begins to rise to help us wake up and prepare for another stressful day. The normal range for blood cortisol
levels is a fairly wide range of 6-23 mcg/dl, but these levels can vary tremendously in response to stress,
illness and even following meals (Bjorntorp 1995, Epel 2001).
Cortisol Levels Throughout the Day
18
16
14
12
10
8
6
4
2
0
4AM
6AM
8AM
10AM
Noon
2PM
4PM
6PM
8PM
10PM
Mid
2AM
Stress and Cortisol
There are three main stages of stress; Acute Stress, Chronic Stress and Adrenal Exhaustion.
Stage 1 Acute stress. When the brain perceives a stressful event, it responds by stimulating hormonal
(endocrine) glands throughout the body to release hormones including both adrenaline and cortisol
(resulting in the fight-or-flight response). Stress causes the rapid mobilization of the body’s energy reserves
of fat, protein, and carbohydrates. Levels of adrenaline and cortisol increase, while DHEA
(dehydroepiandrosterone) and testosterone decrease. Acute stress also typically involves increased heart
rate and blood pressure, increased breathing rate, increased body temperature and sweating, feelings of
anxiety and nervousness, headaches, heartburn and irritability.
Stage 2 Chronic Stress. As acute stress becomes more chronic, cortisol levels continue to increase and
DHEA levels continue to decrease. The dual effect of high cortisol and low DHEA lead to muscle loss and
fat gain and can have detrimental effects on bone and other tissues. Typical symptoms associated with
chronic stress may include weight gain, fatigue, fluctuations in blood sugar, increased appetite,
carbohydrate cravings, and reduced immune system function. Scientific studies have shown that chronic
stress leads to overeating (Bjorntorp 2001, Epel 2001, Peeke 1995). During periods of chronic stress, levels
of both cortisol and insulin rise and together send a potent signal to fat cells to store as much fat as
possible. They also signal fat cells to hold on to fat stores, so stress can reduce the ability of the body to
release fat from fat stores to use for energy. Several recent studies have demonstrated that cortisol
secretion is increased with aging and that elevated cortisol levels reduce sensitivity to insulin. Reduced
insulin sensitivity is clearly linked to obesity, diabetes and Metabolic Syndrome X. The early stages of
chronic stress can be considered more of a “hyper-catabolic” situation characterized by accelerated tissue
destruction.
Stage 3 Adrenal Exhaustion. The later stages of chronic stress cause the body to shift to a “hypo-anabolic”
state where the body’s ability to rebuild vital tissues is impaired. At this later stage, much of the damage
has already be done, so muscle and bone tissues are weaker and a vicious cycle of increased appetite,
reduced caloric expenditure and accelerated fat accumulation occur.
Cortisol can have detrimental effects when there is either too much cortisol or the body is exposed to
cortisol on a regular basis. Scientific evidence shows that chronically elevated cortisol levels are associated
with obesity (Bjorntorp 1999), hypertension (Rosmond 2000), diabetes (Bjorntorp and Rosmond 2000),
fatigue (Rosmond 1999), depression (Raikkonen 1994), moodiness (Epel 1999), irregular menstrual periods
(VanItallie 2001) and increased appetite (Epel 2001, Peeke 1995). Stress-related diseases occur because of
an excessive activation of our stress-response in the brain and the endocrine system to common, everyday
sources of physical and psychological stress.
*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure or prevent any disease.
There are many different ways to help control cortisol levels. Eat a balanced diet, get adequate rest, and
regular exercise can help the body adapt and respond to stressful events. Controlling individual stress
responses with various relaxation techniques can help modulate cortisol secretion and normalize
metabolism. There are a variety of dietary supplements that can help control the hyper-secretion of cortisol.
Studies have shown that some dietary supplements can assist the body mount it’s own adaptive response to
stress and help minimize or control some of the systemic effects of stress. Bringing cortisol levels back into
a normal range will bring caloric expenditure back to normal levels, reduce body fat levels, preserve
muscle mass, reduce appetite, and increase energy levels. Other benefits include reducing cholesterol and
blood sugar, maintaining brain power, reducing bone loss, and strengthening immune function.
PRIMARY ACTIVE CONSTITUENTS
The key active constituents found in Cortitrol include Magnolia bark (Magnolia officinalis), Epimedium
(Epimedium koreanum) Water Extract 6:1, L-Theanine (from Camellia sinensis, Extract 70:1
(TheaPure™), Beta Sitosterol and Phosphatidylserine. The Magnolia bark in Cortitrol is standardized to 2%
Honokiol – a constituent with known anxiolytic properties (Kuribara 2001). Theanine is a unique amino
acid found in the leaves of green tea (Camellia sinensis). Theanine acts as a non-sedating relaxant to help
increase the brain’s production of alpha-waves. Phosphatidylserine (PS) is a phospholipid, a molecule
made up of two fatty acids and a phosphate group attached to a glycerol backbone. Phosphatidylserine is
concentrated in cells of the brain, where it may be related to brain cell function and neurotransmitter
metabolism. Magnolia bark (Magnolia officinalis) is a traditional Chinese medicine used since 100 A.D.
rich in two biphenol compounds, magnolol and honokiol. Epimedium is a genus of 21 related plant species.
Epimedium is grown as an ornamental herb in Asia and the Mediterranean region.
HEALTH BENEFITS
The constituents of Cortitrol address various aspects of cortisol control. Cortitrol combines natural
ingredients that have been scientifically shown to have direct cortisol-balancing effects. Cortitrol helps
provide enhanced feelings of well-being and control in response to stressful situations, and helps improve
performance and increase vigor throughout the day by the anxiolytic effects of magnolia bark and the
relaxation effects of theanine. Cortitrol helps support weight maintenance efforts and allows better mental
concentration and focus through the natural ingredients theanine, epimedium, beta sitosterol and
phosphatidylserine. Epimedium helps restore normal cortisol levels during stress, phosphatidylserine helps
control cortisol elevation during stress, and beta-sitosterol helps reduce cortisol levels during exercise
stress.
Many of the ingredients found in Cortitrol have multiple mechanisms of action to address various aspects
of cortisol control, which are described below.
Phosphatidylserine
Phosphatidylserine (PS) is a phospholipid that is concentrated in the brain cells, where it is thought to be
related to brain-cell function. But it is also found in all cell membranes where it is thought to play key roles
in muscle metabolism and immune-system function. Phosphatidylserine has also been shown to modulate
many aspects of cortisol overproduction, especially following intense exercise.
There is ample scientific evidence that phosphatidylserine supplements can help improve mental function
and depression, even in cases as severe as Alzheimer’s disease and other forms of age-related mental
decline. More recent studies have shown phosphatidylserine to reduce cortisol levels by 15–30 percent
following heavy exercise (Monteleone 1990). Because cortisol is catabolic toward muscle tissue, athletes
frequently use PS supplements to help promote recovery from exercise and help slow muscle loss. Because
of its benefits in improving cognitive function, phosphatidylserine could also be considered a general
antistress nutrient, providing benefits not only for athletes subjected to the physical stress of exercise, but
also for individuals who are under chronic emotional stress from hectic lifestyles, job deadlines, and many
of the other stresses of a modern lifestyle.
*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure or prevent any disease.
Beta-sitosterol
Beta-sitosterol has a structural similarity to cholesterol, but none of the artery-clogging effects. In the diet,
plant oils contain the highest concentration of beta-sitosterol, nuts and seeds contain fairly high levels, and
all fruits and vegetables generally contain some amount of beta-sitosterol. Perhaps the best way to obtain
beta-sitosterol is to eat a diet rich in fruits, vegetables, nuts, and seeds.
Beta-sitosterol appears to help modulate immune function, inflammation, and pain levels through effects on
controlling the production of inflammatory cytokines. In athletes competing in marathons and other
endurance events, beta-sitosterol is known to reduce cortisol levels, maintain DHEA levels, and prevent the
typical suppression of immune-system function seen after endurance events. From test-tube and animal
studies, it appears that beta-sitosterol can influence the structure and function of cell membranes in both
healthy and cancerous tissue. This effect is known to alter cellular signaling pathways that regulate tumor
growth and apoptosis (cell death) and provide a possible explanation for the stimulation of immune
function observed following beta-sitosterol supplementation.
In terms of general immune function, beta-sitosterol has been shown in humans to normalize the function
of T-helper lymphocytes and natural killer cells following stressful events, such as marathon running, that
normally suppress immune-system function. In addition to alleviating much of the postexercise immune
suppression that occurs following endurance competitions, beta-sitosterol has also been shown to normalize
the ratio of catabolic stress hormones (i.e., those that break down tissue, such as cortisol) to anabolic
(rebuilding) hormones such as DHEA. In one study, seventeen endurance runners completed a sixty-eightkilometer run (about forty miles) and afterward received either 60 mg of beta-sitosterol (nine runners) or a
placebo (eight runners) for four weeks. Those runners receiving the beta-sitosterol supplements showed a
significant drop in their cortisol-to-DHEA ratio (indicating less stress) as well as reduced inflammation and
a markedly lower immunosuppression. Using the ultramarathon as a model for overall stress, researchers
concluded that beta-sitosterol is effective in modulating the stress response by managing cortisol levels
within a more normal range.
Magnolia Bark
Magnolia bark (Magnolia officinalis) is a traditional Chinese medicine used since 100 A.D. for treating
stagnation of qi (low energy) as well as a variety of syndromes, such as digestive disturbances caused by
emotional distress and emotional turmoil. The two active compounds, magnolol and honokiol, are thought
to contribute to the primary antistress and cortisol-lowering effects of the plant.
Numerous animal studies have demonstrated honokiol to act as a central nervous system depressant at high
doses, but as a nonsedating anxiolytic (antianxiety and antistress) agent at lower doses. When compared to
pharmaceutical agents such as Valium (diazepam), honokiol appears to be as effective in its antianxiety
activity, yet not nearly as powerful in its sedative ability.
Theanine
Theanine is a unique amino acid found in the leaves of green tea (Camellia sinensis) and acts as a
nonsedating relaxant to help increase the brain’s production of alpha waves. As such, theanine may be
effective for combating tension, stress, and anxiety—without inducing drowsiness. Clinical studies show
that theanine is effective in dosages ranging from 50 to 200 mg per day. Three to four cups of green tea are
expected to contain 100–200 mg of theanine.
In addition to being considered a relaxing substance (in adults), theanine has also been shown to have
benefits for improving learning performance (in mice), and promoting concentration (in students). No
adverse side effects are associated with theanine consumption, making it one of the leading natural choices
for promoting relaxation without the sedating effects of depressant drugs and herbs. When considering the
potential benefits of theanine as an antistress or anticortisol supplement, it is important to distinguish its
nonsedating relaxation benefits from the tranquilizing effects of other “relaxing” supplements such as
valerian and kava, which are actually mild central nervous system depressants.
As mentioned previously, one of the most unique aspects of theanine activity is its ability to increase the
brain’s output of alpha waves. Alpha waves are one the four basic brain-wave patterns (delta, theta, alpha,
*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure or prevent any disease.
and beta) that can be monitored using an electroencephalogram (EEG). Each wave pattern is associated
with a particular oscillating electrical voltage in the brain, and the different brain-wave patterns are
associated with different mental states and states of consciousness (see Table below).
Brain-Wave Oscillation Patterns (Speeds)
Brain-Wave Pattern
Cycles per Second
Mood/Emotional State
Delta
0–4
Deep sleep (stages 3 and 4)
Theta
4–8
Drowsy/light sleep (stages 1 and 2)
Alpha
8–13
Relaxed/wakeful/alert
Beta
13–40
Stress/anxiety/difficulty concentrating
Epimedium
Epimedium is a genus of twenty-one related plant species. Epimedium is grown as an ornamental herb in
Asia and the Mediterranean region, and various species are used for medicinal purposes, including
Epimedium sagittatum, Epimedium brevicornum, Epimedium wushanense, Epimedium koreanum, and
Epimedium pubescens.
The use of epimedium as a medicinal herb dates back to at least 400 A.D. It has been used as a tonic for the
reproductive system (boosting libido and treating impotence) and as a rejuvenating tonic (to relieve
fatigue). Animal studies have shown that epimedium may function like an adaptogen by increasing levels
of epinephrine, norepinephrine, serotonin, and dopamine when they are low (an energy-promoting effect),
but reducing cortisol levels when they are elevated (an antistress effect). There is also evidence that
epimedium can restore low levels of both testosterone and thyroid hormone to their normal levels; this may
account for some of the benefits of epimedium in improving libido. Animal studies using epimedium have
shown a reduction in bone breakdown, an increase in muscle mass, and a loss of body fat—each of which
may be linked to the observed reduction of elevated cortisol to normal levels.
In a series of studies conducted in humans and animals by Chinese researchers, immune-system function
was directly suppressed and bone loss was accelerated by using high-dose glucocorticoids. Subsequent
administration of epimedium extract reduced blood levels of cortisol and improved immune-system
function (in the humans) and slowed bone loss and strengthened bones (in the animals) (Wu 1996).
PROPRIETARY PROCESSING
The combination of quality ingredients, qualified manufacturers, certified independent laboratory
verification, and a continuous drive to supply leading-edge products, ensures our distributors and
consumers the highest quality products available in the industry. The constituents in Cortitrol are
standardized through scientific and analytical methods to ensure that every capsule contains the specific
level of constituents, every time.
Cortitrol is one of the first cortisol-controlling dietary supplements. Cortitrol is a proprietary blend of
ingredients that both lowers cortisol and improves mental function. Cortitrol contains a proprietary mixture
of theanine. Cortitrol is a patent-pending formula for cortisol control.
All ingredients are tested for purity, and where applicable, ingredients are certified pure by microbial
testing, such as tests for Salmonella, E. coli, other coliforms, Staphylococcus aureus, total plate counts,
yeasts, molds and pesticide residues. Our manufacturers go through a detailed selection and certification
process to assure their compliance with Good Manufacturing Practice (GMP) standards set by the Food and
Drug Administration (FDA).
SIDE EFFECTS
No known side effects at recommended dosage.
SAFETY AND TOXICITY
*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure or prevent any disease.
Cortitrol is safe and well tolerated at the recommended dosage. L-theanine has been approved in Japan for
unlimited use in all foods, except infant foods, after favorable toxicology studies. There are no limitations
to duration of administration or known adverse drug interactions (Mason 2001).
CONTRAINDICATIONS/DRUG INTERACTIONS
If you are pregnant or lactating, or taking a prescription medication, or allergic to any component of this
product, please consult a physician prior to use. Because Cortitrol is indicated for stress relief, consult a
physician if you are taking prescription "anti-stress" medications such as anxiolytics, sedatives, or
hypnotics. Consult a physician if you are taking other CNS depressants, tricyclic antidepressants, antiepileptics, muscle relaxants, anticoagulants, corticosteroids and quinalone antibiotics. Use of l-theanine
concomitantly with chemotherapeutic agents must be done under medical supervision. L-theanine may
enhance the effects of doxorubicin, idarubicin, adriamycin, and picarubicin and may ameliorate some of
their side effects (PDR for Nutritional Supplements 2001, Sadzuka 1996, Sugiyma 1998, 1999). This
supplement should be discontinued two weeks prior to surgery.
DIRECTIONS FOR USE
As a dietary supplement, take two to three capsules daily. Take two (2) capsules with your evening meal.
For optimal results take an additional (1) capsule with your morning meal.
HOW SUPPLIED
Cortitrol is supplied in a 20-30 day supply of 60 capsules.
STORAGE
Store in a cool, dry place. Avoid excessive heat. Protect from light.
SHELF LIFE
Expiration date and lot code numbers are stamped on the bottle.
WARNINGS
Keep out of reach of children. If you are pregnant or nursing, or taking a prescription medication, consult a
physician before using this product.
REFERENCES
MAGNOLIA
1.
Hou YC, Chao PD, Chen SY. Honokiol and magnolol increased hippocampal acetylcholine release in freely-moving rats. Am J
Chin Med. 2000;28(3-4):379-84.
2.
Kuribara H, Iwata H, Tomioka H, Takahashi R, Goto K, Murohashi N, Koya S. The anxiolytic effect of Sho-ju-sen, a Japanese
herbal medicine, assessed by an elevated plus-maze test in mice. Phytother Res. 2001 Mar;15(2):142-7.
3.
Kuribara H, Kishi E, Hattori N, Okada M, Maruyama Y. The anxiolytic effect of two oriental herbal drugs in Japan attributed to
honokiol from magnolia bark. J Pharm Pharmacol. 2000 Nov;52(11):1425-9.
4.
Kuribara H, Kishi E, Hattori N, Yuzurihara M, Maruyama Y. Application of the elevated plus-maze test in mice for evaluation
of the content of honokiol in water extracts of magnolia. Phytother Res. 1999 Nov;13(7):593-6.
5.
Kuribara H, Kishi E, Kimura M, Weintraub ST, Maruyama Y. Comparative assessment of the anxiolytic-like activities of
honokiol and derivatives. Pharmacol Biochem Behav. 2000 Nov;67(3):597-601.
6.
Kuribara H, Kishi E, Maruyama Y. Does dihydrohonokiol, a potent anxiolytic compound, result in the development of
benzodiazepine-like side effects? J Pharm Pharmacol. 2000 Aug;52(8):1017-22.
7.
Kuribara H, Stavinoha WB, Maruyama Y. Behavioural pharmacological characteristics of honokiol, an anxiolytic agent present
in extracts of Magnolia bark, evaluated by an elevated plus-maze test in mice. J Pharm Pharmacol. 1998 Jul;50(7):819-26.
8.
Kuribara H, Stavinoha WB, Maruyama Y. Honokiol, a putative anxiolytic agent extracted from magnolia bark, has no diazepamlike side-effects in mice. J Pharm Pharmacol. 1999 Jan;51(1):97-103.
9.
Maruyama Y, Kuribara H, Kishi E, Weintraub ST, Ito Y. Confirmation of the anxiolytic-like effect of dihydrohonokiol
following behavioural and biochemical assessments. J Pharm Pharmacol. 2001 May;53(5):721-5.
10. Maruyama Y, Kuribara H, Morita M, Yuzurihara M, Weintraub ST. Identification of magnolol and honokiol as anxiolytic agents
in extracts of saiboku-to, an oriental herbal medicine. J Nat Prod. 1998 Jan;61(1):135-8.
11. Ueda J, Asaka N, Tanaka I, Hayashi Y, Hirose Y, Momma N, Yasuda T, Ohsawa K. A simultaneous determination of honokiol
and mangolol in Oriental pharmaceutical decoctions containing magnolia bark by ion-pair high-performance liquid
chromatography. II. Yakugaku Zasshi. 1993 Dec;113(12):894-6.
12. Ueda J, Momma N, Ohsawa K. A simultaneous determination of honokiol and magnolol in oriental pharmaceutical decoctions
containing magnolia bark by ion-pair high-performance liquid chromatography. Yakugaku Zasshi. 1993 Feb;113(2):155-8.
*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure or prevent any disease.
13. Watanabe K, Watanabe HY, Goto Y, Yamamoto N, Yoshizaki M. Studies on the active principles of magnolia bark. Centrally
acting muscle relaxant activity of magnolol and honokiol. Jpn J Pharmacol. 1975 Oct;25(5):605-7.
EPIMEDIUM
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
Ascott-Evans BH. Prevention of corticosteroid-induced osteoporosis. S Afr Med J. 1996 Aug;86(8 Suppl):1025-6.
Cai D, Shen S, Chen X. Clinical and experimental research of Epimedium brevicornum in relieving neuroendocrinoimmunological effect inhibited by exogenous glucocorticoid. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1998 Jan;18(1):4-7.
Chen C, Sha M, Yang S, Zhang Z. Quantitative study of magnoflorine in Epimedium koreanum Nakai. Zhongguo Zhong Yao Za
Zhi. 1996 Nov;21(11):681-2, 704.
Chen MD, Kuang AK, Chen JL. Influence of yang-restoring herb medicines upon metabolism of thyroid hormone in normal rats
and a drug administration schedule. Zhong Xi Yi Jie He Za Zhi. 1989 Feb;9(2):93-5, 70.
Gao B, Yu J, Xiao P. Chemical constituents from the aerial part of Epimedium brevicornum Maxim. Zhongguo Zhong Yao Za
Zhi. 1996 May;21(5):290-2, 319.
Guo B, Xiao P. Determination of flavonoids in different parts of five epimedium plants. Zhongguo Zhong Yao Za Zhi. 1996
Sep;21(9):523-5, 574.
Huang HC, Chen XH. Analysis and counter measure prevention and treatment of osteoporosis with traditional Chinese medicine.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 1996 Aug;16(8):498-500.
Jia X, Wu J, Mao Q. Chemical constituents of the root of Epimedium acumiantum Franch. Zhongguo Zhong Yao Za Zhi. 1998
Mar;23(3):162-4, 192.
Kuang AK, Chen JL, Chen MD. Effects of yang-restoring herb medicines on the levels of plasma corticosterone, testosterone
and triiodothyronine. Zhong Xi Yi Jie He Za Zhi. 1989 Dec;9(12):737-8, 710.
Li WK, Xiao PG, Tu GZ, Ma LB, Zhang RY. Flavonol glycosides from Epimedium koreanum. Phytochemistry. 1995
Jan;38(1):263-5.
Liang HR, Siren H, Jyske P, Reikkola ML. Characterization of flavonoids in extracts from four species of Epimedium by
micellar electrokinetic capillary chromatography with diode-array detection. J Chromatogr Sci. 1997 Mar;35(3):117-25.
Liang HR, Vuorela P, Vuorela H, Hiltunen R. Isolation and immunomodulatory effect of flavonol glycosides from Epimedium
hunanense. Planta Med. 1997 Aug;63(4):316-9.
Liao HJ, Chen XM, Li WG. Effect of Epimedium sagittatum on quality of life and cellular immunity in patients of hemodialysis
maintenance. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1995 Apr;15(4):202-4.
Liu ZY, Yang YG, Zheng B. Effect of improving memory and inhibiting acetylcholinesterase activity by invigorating-qi and
warming-yang recipe. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1993 Nov;13(11):675-6, 646.
Meng X, Zeng N, Zhang Y, Lai X, Ren C, Cheng L. Effect of active constituents of Herba Epimedii on hypothalamic
monoamine neurotransmitters and other brain functions in aging rats. Zhongguo Zhong Yao Za Zhi. 1996 Nov;21(11):683-5
inside back cover.
Mier RJ. Prevention of corticosteroid induced osteoporosis. J Rheumatol. 1997 Feb;24(2):407.
Niu R. Action of the drug Herba Epimedii on testosterone of the mouse plasma and its accessory sexual organ before and after
processing. Zhongguo Zhong Yao Za Zhi. 1989 Sep;14(9):530-2, 574.
Sun P, Wen Y, Xu Y, Pei Y, Chen Y, Shimizu N, Takeda T. The chemical constituents of Epimedium koreanum Nakai. Yao
Xue Xue Bao. 1998 Dec;33(12):919-22.
Sun PY, Chen YJ, Wen Y, Pei YP, Liu ZH, Yao XS, Takeda T, Ogihara Y. Structure determination of korepimedoside A and
korepimedoside B from Epimedium koreanum Nakai. Yao Xue Xue Bao. 1996;31(8):602-6.
Wang C, Li Y, Wang Y. A review of pharmacological study on Epimedium grandiflorum Morr and its active constituents.
Zhongguo Zhong Yao Za Zhi. 1998 Mar;23(3):183-5.
Wu T, Cui L, Zhang Z, Chen Z, Li Q, Liao J, Huang L. Experimental study on antagonizing action of herba Epimedii on side
effects induced by glucocorticoids. Zhongguo Zhong Yao Za Zhi. 1996 Dec;21(12):748-51, 763.
Wu T, Liao J, Li Q. Experimental study on zhuanggu shengbao in preventing hormone-induced osteoporosis of rats. Zhongguo
Zhong Xi Yi Jie He Za Zhi. 1996 Feb;16(2):102-4.
Xie H, Wu T, Huang L, Li C. Preventive effect of gubao on hydrocortisone-induced osteoporosis in rats. Zhongguo Zhong Yao
Za Zhi. 1997 Apr;22(4):238-40, 256.
Xu M, Cheng Z. Advances in the chemical study of Epimedium. Zhongguo Zhong Yao Za Zhi. 1997 Oct;22(10):631-2.
Yu L, Li H, Huang G, Bai Y, Dong Y. Clinical observations on treatment of 120 cases of coronary heart disease with herba
epimedii. J Tradit Chin Med. 1992 Mar;12(1):30-4.
Yu S, Chen K, Li S, Zhang K. In vitro and in vivo studies of the effect of a Chinese herb medicine on osteoclastic bone
resorption. Chin J Dent Res. 1999 Feb;2(1):7-11.
Zheng J, Luo Y, Meng X, Sun Y, Zhang Y, Dong X, Shen W, Yang A, Xia C. Effects of Sichuan herba Epimedii on the
concentration of plasma middle molecular substances and sulfhydryl group of "yang-deficiency" model animal. Zhongguo
Zhong Yao Za Zhi. 1995 Apr;20(4):238-9, 254.
THEANINE
1.
2.
3.
4.
Kakuda T, Nozawa A, Unno T, Okamura N, Okai O. Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in
the rat. Biosci Biotechnol Biochem. 2000 Feb;64(2):287-93.
Kakuda T, Yanase H, Utsunomiya K, Nozawa A, Unno T, Kataoka K. Protective effect of gamma-glutamylethylamide
(theanine) on ischemic delayed neuronal death in gerbils. Neurosci Lett. 2000 Aug 11;289(3):189-92.
Kimura R, Kurita M, Murata T. Influence of alkylamides of glutamic acid and related compounds on the central nervous system.
III. Effect of theanine on spontaneous activity of mice. Yakugaku Zasshi. 1975 Jul;95(7):892-5.
Kimura R, Murata T. Effect of theanine on norepinephrine and serotonin levels in rat brain. Chem Pharm Bull (Tokyo). 1986
Jul;34(7):3053-7.
*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure or prevent any disease.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
Kimura R, Murata T. Influence of alkylamides of glutamic acid and related compounds on the central nervous system. IV. Effect
of theanine on adenosine 3',5'-monophosphate formation in rat cerebral cortex. Chem Pharm Bull (Tokyo). 1980 Feb;28(2):6646.
Kimura R, Murata T. Influence of alkylamides of glutamic acid and related compounds on the central nervous system. I. Central
depressant effect of theanine. Chem Pharm Bull (Tokyo). 1971 Jun;19(6):1257-61.
Shinozaki H, Ishida M. Theanine as a glutamate antagonist at a crayfish neuromuscular junction. Brain Res. 1978 Jul
28;151(1):215-9.
Terashima T, Takido J, Yokogoshi H. Time-dependent changes of amino acids in the serum, liver, brain and urine of rats
administered with theanine. Biosci Biotechnol Biochem. 1999 Apr;63(4):615-8.
Unno T, Suzuki Y, Kakuda T, Hayakawa T, Tsuge H. Metabolism of theanine, gamma-glutamylethylamide, in rats. J Agric
Food Chem. 1999 Apr;47(4):1593-6.
Yagyu T, Wackermann J, Kinoshita T, Hirota T, Kochi K, Kondakor I, Koenig T, Lehmann D. Chewing-gum flavor affects
measures of global complexity of multichannel EEG. Neuropsychobiology. 1997;35(1):46-50.
Yokogoshi H, Kato Y, Sagesaka YM, Takihara-Matsuura T, Kakuda T, Takeuchi N. Reduction effect of theanine on blood
pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Biosci Biotechnol Biochem. 1995 Apr;59(4):615-8.
Yokogoshi H, Kobayashi M, Mochizuki M, Terashima T. Effect of theanine, r-glutamylethylamide, on brain monoamines and
striatal dopamine release in conscious rats. Neurochem Res. 1998 May;23(5):667-73.
Yokogoshi H, Kobayashi M. Hypotensive effect of gamma-glutamylmethylamide in spontaneously hypertensive rats. Life Sci.
1998;62(12):1065-8.
Yokogoshi H, Mochizuki M, Saitoh K. Theanine-induced reduction of brain serotonin concentration in rats. Biosci Biotechnol
Biochem. 1998 Apr;62(4):816-7.
Yokogoshi H, Terashima T. Effect of theanine, r-glutamylethylamide, on brain monoamines, striatal dopamine release and some
kinds of behavior in rats. Nutrition. 2000 Sep;16(9):776-7.
PHOSPHATIDYLSERINE
1.
2.
3.
4.
5.
6.
7.
8.
Benton D, Donohoe RT, Sillance B, Nabb S. The influence of phosphatidylserine supplementation on mood and heart rate when
faced with an acute stressor. Nutr Neurosci. 2001;4(3):169-78.
Heiman AS, Crews FT. Hydrocortisone inhibits phorbol ester stimulated release of histamine and arachidonic acid from rat mast
cells. Biochem Biophys Res Commun. 1985 Jul 31;130(2):640-5.
Kelly GS. Nutritional and botanical interventions to assist with the adaptation to stress. Altern Med Rev. 1999 Aug;4(4):249-65.
Khalsa DS. Integrated medicine and the prevention and reversal of memory loss. Altern Ther Health Med. 1998 Nov;4(6):38-43.
Melby JM, Wennhold AR, Nelson DH. Corticosteroid-induced lipid changes in rat liver microsomes. Endocrinology. 1981
Sep;109(3):920-3.
Monteleone P, Beinat L, Tanzillo C, Maj M, Kemali D. Effects of phosphatidylserine on the neuroendocrine response to physical
stress in humans. Neuroendocrinology. 1990 Sep;52(3):243-8.
Monteleone P, Maj M, Beinat L, Natale M, Kemali D. Blunting by chronic phosphatidylserine administration of the stressinduced activation of the hypothalamo-pituitary-adrenal axis in healthy men. Eur J Clin Pharmacol. 1992;42(4):385-8.
Nishikawa T, Yoshida A, Tamura Y, Yoshida S. Involvement of protein kinase C in the regulation of cortisol production by
guinea pig adrenocortical cells. Horm Metab Res. 1990 Jan;22(1):29-32.
BETA-SITOSTEROL
1.
2.
3.
4.
5.
Bouic PJ, Clark A, Lamprecht J, Freestone M, Pool EJ, Liebenberg RW, Kotze D, van Jaarsveld PP. The effects of B-sitosterol
(BSS) and B-sitosterol glucoside (BSSG) mixture on selected immune parameters of marathon runners: inhibition of post
marathon immune suppression and inflammation. Int J Sports Med. 1999 May;20(4):258-62.
Bouic PJ, Lamprecht JH. Plant sterols and sterolins: a review of their immune-modulating properties. Altern Med Rev. 1999
Jun;4(3):170-7.
Bouic PJ. The role of phytosterols and phytosterolins in immune modulation: a review of the past 10 years. Curr Opin Clin Nutr
Metab Care. 2001 Nov;4(6):471-5.
Davis RH, DiDonato JJ, Johnson RW, Stewart CB. Aloe vera, hydrocortisone, and sterol influence on wound tensile strength
and anti-inflammation. J Am Podiatr Med Assoc. 1994 Dec;84(12):614-21.
No authors listed. Monograph. Plant sterols and sterolins. Altern Med Rev. 2001 Apr;6(2):203-6.
STRESS / CORTISOL & WEIGHT MAINTENANCE
1.
2.
Bjorntorp P, Rosmond R. Hypothalamic origin of the metabolic syndrome X. Ann N Y Acad Sci. 1999 Nov 18;892:297-307.
Bjorntorp P, Rosmond R. Neuroendocrine abnormalities in visceral obesity. Int J Obes Relat Metab Disord. 2000 Jun;24 Suppl
2:S80-5.
3.
Bjorntorp P, Rosmond R. Obesity and cortisol. Nutrition. 2000 Oct;16(10):924-36.
4.
Bjorntorp P, Rosmond R. The metabolic syndrome--a neuroendocrine disorder? Br J Nutr. 2000 Mar;83 Suppl 1:S49-57.
5.
Bjorntorp P, Rossner S, Udden J. "Consolatory eating" is not a myth. Stress-induced increased cortisol levels result in leptinresistant obesity. Lakartidningen. 2001 Nov 28;98(48):5458-61.
6.
Bjorntorp P. Body fat distribution, insulin resistance, and metabolic diseases. Nutrition. 1997 Sep;13(9):795-803.
7.
Bjorntorp P. Endocrine abnormalities of obesity. Metabolism. 1995 Sep;44(9 Suppl 3):21-3.
8.
Bjorntorp P. The origins and consequences of obesity. Diabetes. Ciba Found Symp. 1996;201:68-80; discussion 80-9, 188-93.
9.
Duclos M, Corcuff JB, Etcheverry N, Rashedi M, Tabarin A, Roger P. Abdominal obesity increases overnight cortisol excretion.
J Endocrinol Invest. 1999 Jun;22(6):465-71.
10. Epel E, Lapidus R, McEwen B, Brownell K. Stress may add bite to appetite in women: a laboratory study of stress-induced
cortisol and eating behavior. Psychoneuroendocrinology. 2001 Jan;26(1):37-49.
*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure or prevent any disease.
11. Epel EE, Moyer AE, Martin CD, Macary S, Cummings N, Rodin J, Rebuffe-Scrive M. Stress-induced cortisol, mood, and fat
distribution in men. Obes Res. 1999 Jan;7(1):9-15.
12. Epel ES, McEwen B, Seeman T, Matthews K, Castellazzo G, Brownell KD, Bell J, Ickovics JR. Stress and body shape: stressinduced cortisol secretion is consistently greater among women with central fat. Psychosom Med. 2000 Sep-Oct;62(5):623-32.
13. Esposito-Del Puente A, Lillioja S, Bogardus C, McCubbin JA, Feinglos MN, Kuhn CM, Surwit RS. Glycemic response to stress
is altered in euglycemic Pima Indians. Int J Obes Relat Metab Disord. 1994 Nov;18(11):766-70.
14. Gelfand RA, Matthews DE, Bier DM, Sherwin RS. Role of counterregulatory hormones in the catabolic response to stress. J
Clin Invest. 1984 Dec;74(6):2238-48.
15. Golub MS. The adrenal and the metabolic syndrome. Curr Hypertens Rep. 2001 Apr;3(2):117-20.
16. Hagan MM, Havel PJ, Seeley RJ, Woods SC, Ekhator NN, Baker DG, Hill KK, Wortman MD, Miller AH, Gingerich RL,
Geracioti TD. Cerebrospinal fluid and plasma leptin measurements: covariability with dopamine and cortisol in fasting humans.
J Clin Endocrinol Metab. 1999 Oct;84(10):3579-85.
17. Kaye SA, Folsom AR. Is serum cortisol associated with body fat distribution in postmenopausal women? Int J Obes. 1991
Jul;15(7):437-9.
18. Keltikangas-Jarvinen L, Raikkonen K, Hautanen A, Adlercreutz H. Vital exhaustion, anger expression, and pituitary and
adrenocortical hormones. Implications for the insulin resistance syndrome. Arterioscler Thromb Vasc Biol. 1996 Feb;16(2):27580.
19. Lemieux AM, Coe CL. Abuse-related posttraumatic stress disorder: evidence for chronic neuroendocrine activation in women.
Psychosom Med. 1995 Mar-Apr;57(2):105-15.
20. Ljung T, Andersson B, Bengtsson BA, Bjorntorp P, Marin P. Inhibition of cortisol secretion by dexamethasone in relation to
body fat distribution: a dose-response study. Obes Res. 1996 May;4(3):277-82.
21. Ljung T, Holm G, Friberg P, Andersson B, Bengtsson BA, Svensson J, Dallman M, McEwen B, Bjorntorp P. The activity of the
hypothalamic-pituitary-adrenal axis and the sympathetic nervous system in relation to waist/hip circumference ratio in men.
Obes Res. 2000 Oct;8(7):487-95.
22. Marin P, Darin N, Amemiya T, Andersson B, Jern S, Bjorntorp P. Cortisol secretion in relation to body fat distribution in obese
premenopausal women. Metabolism. 1992 Aug;41(8):882-6.
23. Marniemi J, Kronholm E, Aunola S, Toikka T, Mattlar CE, Koskenvuo M, Ronnemaa T. Visceral fat and psychosocial stress in
identical twins discordant for obesity. J Intern Med. 2002 Jan;251(1):35-43.
24. Martin-Du Pan RC, Heraief E. Ten questions on the causes and consequences of obesity: stress hormones. Rev Med Suisse
Romande. 2001 Jan;121(1):51-5.
25. McCarty MF. Modulation of adipocyte lipoprotein lipase expression as a strategy for preventing or treating visceral obesity. Med
Hypotheses. 2001 Aug;57(2):192-200.
26. Nelson TL, Palmer RF, Pedersen NL, Miles TP. Psychological and behavioral predictors of body fat distribution: age and gender
effects. Obes Res. 1999 Mar;7(2):199-207.
27. Pasquali R, Anconetani B, Chattat R, Biscotti M, Spinucci G, Casimirri F, Vicennati V, Carcello A, Labate AM. Hypothalamicpituitary-adrenal axis activity and its relationship to the autonomic nervous system in women with visceral and subcutaneous
obesity: effects of the corticotropin-releasing factor/arginine-vasopressin test and of stress. Metabolism. 1996 Mar;45(3):351-6.
28. Pasquali R, Vicennati V. Activity of the hypothalamic-pituitary-adrenal axis in different obesity phenotypes. Int J Obes Relat
Metab Disord. 2000 Jun;24 Suppl 2:S47-9.
29. Peeke PM, Chrousos GP. Hypercortisolism and obesity. Ann N Y Acad Sci. 1995 Dec 29;771:665-76.
30. Raber J. Detrimental effects of chronic hypothalamic-pituitary-adrenal axis activation. From obesity to memory deficits. Mol
Neurobiol. 1998 Aug;18(1):1-22.
31. Raikkonen K, Hautanen A, Keltikangas-Jarvinen L. Association of stress and depression with regional fat distribution in healthy
middle-aged men. J Behav Med. 1994 Dec;17(6):605-16.
32. Rosmond R, Bjorntorp P. Blood pressure in relation to obesity, insulin and the hypothalamic-pituitary-adrenal axis in Swedish
men. J Hypertens. 1998 Dec;16(12 Pt 1):1721-6.
33. Rosmond R, Bjorntorp P. Endocrine and metabolic aberrations in men with abdominal obesity in relation to anxio-depressive
infirmity. Metabolism. 1998 Oct;47(10):1187-93.
34. Rosmond R, Bjorntorp P. Occupational status, cortisol secretory pattern, and visceral obesity in middle-aged men. Obes Res.
2000 Sep;8(6):445-50.
35. Rosmond R, Bjorntorp P. Psychosocial and socio-economic factors in women and their relationship to obesity and regional body
fat distribution. Int J Obes Relat Metab Disord. 1999 Feb;23(2):138-45.
36. Rosmond R, Bjorntorp P. The hypothalamic-pituitary-adrenal axis activity as a predictor of cardiovascular disease, type 2
diabetes and stroke. J Intern Med. 2000 Feb;247(2):188-97.
37. Rosmond R, Bjorntorp P. The interactions between hypothalamic-pituitary-adrenal axis activity, testosterone, insulin-like growth
factor I and abdominal obesity with metabolism and blood pressure in men. Int J Obes Relat Metab Disord. 1998
Dec;22(12):1184-96.
38. Rosmond R, Bjorntorp P. The role of antidepressants in the treatment of abdominal obesity. Med Hypotheses. 2000
Jun;54(6):990-4.
39. Rosmond R, Chagnon M, Bouchard C, Bjorntorp P. A missense mutation in the human melanocortin-4 receptor gene in relation
to abdominal obesity and salivary cortisol. Diabetologia. 2001 Oct;44(10):1335-8.
40. Rosmond R, Chagnon YC, Holm G, Chagnon M, Perusse L, Lindell K, Carlsson B, Bouchard C, Bjorntorp P. A glucocorticoid
receptor gene marker is associated with abdominal obesity, leptin, and dysregulation of the hypothalamic-pituitary-adrenal axis.
Obes Res. 2000 May;8(3):211-8.
41. Rosmond R, Dallman MF, Bjorntorp P. Stress-related cortisol secretion in men: relationships with abdominal obesity and
endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab. 1998 Jun;83(6):1853-9.
42. Rosmond R, Eriksson E, Bjorntorp P. Personality disorders in relation to anthropometric, endocrine and metabolic factors. J
Endocrinol Invest. 1999 Apr;22(4):279-88.
43. Rosmond R, Holm G, Bjorntorp P. Food-induced cortisol secretion in relation to anthropometric, metabolic and haemodynamic
variables in men. Int J Obes Relat Metab Disord. 2000 Apr;24(4):416-22.
*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure or prevent any disease.
44. Sokolov EI, Khovanskaia TP, Novikova IV, Baluda MV. Interaction of adrenocorticotropic hormone, cortisol and insulin during
emotional tension among ischemic heart disease patients. Kardiologiia. 1985 Dec;25(12):81-4.
45. Vanitallie TB. Stress: a risk factor for serious illness. Metabolism. 2002 Jun;51(6 Suppl 1):40-5.
46. Voznesenskaia TG, Solov'eva AD, Fokina NM. Psycho-endocrine interrelations in patients in a state of emotional stress during
cerebral obesity. Probl Endokrinol (Mosk). 1989 Jan-Feb;35(1):3-7.
*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure or prevent any disease.